CAVIN1

Chr 17AR

caveolae associated protein 1

Also known as: CAVIN, CGL4, FKSG13, PTRF, cavin-1

NCBI Gene: 284119ENSG00000177469UniProt: Q6NZI2

This gene encodes a protein that enables the dissociation of paused ternary polymerase I transcription complexes from the 3' end of pre-rRNA transcripts. This protein regulates rRNA transcription by promoting the dissociation of transcription complexes and the reinitiation of polymerase I on nascent rRNA transcripts. This protein also localizes to caveolae at the plasma membrane and is thought to play a critical role in the formation of caveolae and the stabilization of caveolins. This protein translocates from caveolae to the cytoplasm after insulin stimulation. Caveolae contain truncated forms of this protein and may be the site of phosphorylation-dependent proteolysis. This protein is also thought to modify lipid metabolism and insulin-regulated gene expression. Mutations in this gene result in a disorder characterized by generalized lipodystrophy and muscular dystrophy. [provided by RefSeq, Nov 2009]

Primary Disease Associations & Inheritance

Lipodystrophy, congenital generalized, type 4MIM #613327
AR
191
ClinVar variants
22
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CAVIN1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
22 Pathogenic / Likely Pathogenic· 96 VUS of 191 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.08LOEUF
pLI 0.005
Z-score 1.40
OE 0.51 (0.27–1.08)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.38Z-score
OE missense 0.76 (0.67–0.85)
195 obs / 257.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.51 (0.27–1.08)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.76 (0.67–0.85)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.88
0≤1.21.6
LoF obs/exp: 5 / 9.7Missense obs/exp: 195 / 257.1Syn Z: 1.08

ClinVar Variant Classifications

191 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic6
VUS96
Likely Benign39
Benign21
Conflicting11
16
Pathogenic
6
Likely Pathogenic
96
VUS
39
Likely Benign
21
Benign
11
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
0
7
0
16
Likely Pathogenic
3
0
3
0
6
VUS
0
66
25
5
96
Likely Benign
0
2
17
20
39
Benign
0
0
20
1
21
Conflicting
—11
Total12687226189

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CAVIN1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Lipodystrophy, congenital generalized, type 4

MIM #613327

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The spectrum of rippling muscle disease.
Rashed HR et al.·Muscle Nerve
2025Review
Caveola-forming proteins and prostate cancer.
Nassar ZD et al.·Cancer Metastasis Rev
2020Review
Proteomics of colorectal tumors identifies the role of CAVIN1 in tumor relapse.
Martinez-Val A et al.·Mol Syst Biol
2025
Caveolar and non-Caveolar Caveolin-1 in ocular homeostasis and disease.
Enyong EN et al.·Prog Retin Eye Res
2022Review
Homotrimer cavin1 interacts with caveolin1 to facilitate tumor growth and activate microglia through extracellular vesicles in glioma.
Wang L et al.·Theranostics
2020
A new mutation in the CAVIN1/PTRF gene in two siblings with congenital generalized lipodystrophy type 4: case reports and review of the literature.
Mancioppi V et al.·Front Endocrinol (Lausanne)
2023Review
Integrated Analysis to Reveal Heterogeneity of Tumor-Associated Neutrophils in Glioma.
Wang W et al.·Cancer Med
2025
Muscular dystrophy in PTFR/cavin-1 null mice.
Ding SY et al.·JCI Insight
2017
Integrated profiling identifies caveolae-associated protein 1 as a prognostic biomarker of malignancy in glioblastoma patients.
Guo Q et al.·CNS Neurosci Ther
2019Cohort
The worldwide mutational landscape of Berardinelli-Seip congenital lipodystrophy.
Craveiro Sarmento AS et al.·Mutat Res Rev Mutat Res
2019Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools